The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p

The yeast nonchromosomal gene [URE3] is due to a prion form of the nitrogen regulatory protein Ure2p. It is a negative regulator of nitrogen catabolis m and acts by inhibiting the transcription factor Gln3p. Ure2p residues 1-8 0 are necessary for prion generation and propagation. The C-terminal fragme nt retains nitrogen regulatory activity, albeit somewhat less efficiently t han the full-length protein, and it also lowers the frequency of prion gene ration. The crystal structure of this C-terminal fragment, Ure2p(97-354), a t 2.3 A resolution is described here. It adopts the same fold as the glutat hione S-transferase superfamily. consistent with their sequence similarity. However, Ure2p(97-354) lacks a properly positioned catalytic residue that is required for S-transferase activity. Residues within this regulatory fra gment that have been indicated by mutational studies to influence prion gen eration have been mapped onto the three-dimensional structure, and possible implications for prion activity are discussed.